Parasites on the Clock—How Malaria Races against Mosquito Reproduction

NIAID Now | April 12, 2019

Malaria sporozoites, the infectious form of the malaria parasite that is injected into people by mosquitoes.

Credit: NIAID

Malaria, which kills more than 420,000 people worldwide each year, is caused by a tiny parasite that infects human livers and red blood cells. Without the Anopheles mosquitoes that carry the malaria parasites (such as Plasmodium falciparum) in their guts and salivary glands, the disease would have no way of spreading. By studying the interactions between the parasites and their mosquito vectors, scientists hope to find new ways of preventing malaria transmission. In a new paper published in Cell, NIAID-supported researchers examine how the mosquito’s reproductive cycle and the steroid hormones associated with it, influence the development of the malaria parasites inside the mosquito’s gut.

From the moment a mosquito takes a blood meal containing malaria parasites, the parasites are in a race against time. In the wild, a female mosquito normally lives no more than two or three weeks. If the mosquito dies, the malaria parasites die with it. This puts the parasite on a tight schedule: it needs enough time inside the mosquito’s gut to complete several stages of its life cycle. After ten to fourteen days, thousands of tiny sporozoites migrate into the mosquito’s saliva glands, ready to be injected into another human during the mosquito’s next meal.

The parasites can speed up their development by leeching off the mosquito’s internal nutrients. This gives them a better chance of being transmitted to a new host before the mosquito lays its eggs and dies. However, scientists suspected that this might cause the mosquito to lay fewer eggs—and, consequently, leave fewer mosquitoes in the future to transport malaria parasites.

To investigate this paradox, the researchers examined the interactions between the mosquito and the parasite. They studied mosquitoes without fully functioning ovaries, tracked steroid hormone levels in female mosquitos, and dissected mosquito midguts and salivary glands to observe the parasites within. They found that disrupting a mosquito steroid hormone called 20E, which is partially responsible for regulating the mosquito’s egg production, also affects the parasites. When the female is not actively preparing to lay eggs, the parasites draw on their insect vector’s stored nutrients in order to grow faster. However, when the female mosquito is preparing to lay eggs, the parasites switch gears: they grow more slowly, but are more abundant.

Surprisingly, this process does not affect the number of eggs that the mosquito lays. The researchers suggest that the malaria parasite has evolved to only use nutrients that the mosquito does not need for egg production. Thus, the parasites are able to increase the likelihood that they will reach a new human host, while also ensuring that their own descendants will have a healthy population of mosquitoes to transport them when the time comes. This interaction between the parasites and their vectors should be taken into account when developing methods of malaria control, the researchers say: Using mosquito suppression systems that decrease female mosquito fertility or disrupt mosquitoes’ ability to digest their blood meals may not stop the spread of malaria and may even lead to an increase in malaria cases.


K Werling et al. Steroid hormone function controls non-competitive Plasmodium development in AnophelesCell DOI: 10.1016/j.cell.2019.02.036 (2019)

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